title: TWEAK is expressed at the cell surface of monocytes during multiple sclerosis.
abstract: The TNF superfamily ligand, TNF-like weak inducer of apoptosis (TWEAK), regulates cellular responses ranging from proliferation to cell death in a manner highly dependent on the cell type and the microenvironmental context. We have shown previously that treatment of experimental autoimmune encephalomyelitis mice after the priming phase with neutralizing anti-TWEAK antibodies results in a reduction in the severity of the disease and leukocyte infiltration. To further characterize TWEAK/fibroblast growth factor-inducible 14-kDa protein (Fn14) involvement during multiple sclerosis (MS), we evaluated in MS patients and controls: TWEAK and Fn14 expression on PBMC and soluble TWEAK concentration in serum and cerebrospinal fluid (CSF). Thirty-six consecutive patients were enrolled, including 11 patients with relapsing-remitting MS, 11 with a clinical isolated syndrome suggestive of MS (CISSMS), and 14 controls with non-MS diseases. Intracellular TWEAK could be observed in lymphocytes and/or monocytes in all groups of patients. None of the 36 patients displayed TWEAK expression at the cell surface of lymphocytes. In contrast, 12 out of the 36 patients were positive for membrane TWEAK expression on their monocytes. Among these patients, eight were from the CISSMS group. Fn14 was not detected in PBMC. The soluble form of TWEAK is detectable in serum and CSF of patients, and TWEAK concentrations were not statistically different between the disease groups. We demonstrated for the first time that TWEAK is expressed at the cell surface of monocytes during MS, especially in the CISSMS group. Our results support the proposal that TWEAK could be a target for antibody therapy in MS.
authors.affiliation: Neurobioligie des Interactions Cellulaires et Neurophysiopathologie, CNRS UMR 6184, IFR Jean Roche, 51 Bd Pierre Dramard, 13 916 Marseille Cedex 20, France. sophie.jego-desplat@ap-hm.fr
authors.forename: Sophie
authors.initials: S
authors.lastname: Desplat-Jégo
authors.forename: Lionel
authors.initials: L
authors.lastname: Feuillet
authors.forename: Rita
authors.initials: R
authors.lastname: Creidy
authors.forename: Irina
authors.initials: I
authors.lastname: Malikova
authors.forename: Roselyne
authors.initials: R
authors.lastname: Rance
authors.forename: Michel
authors.initials: M
authors.lastname: Khrestchatisky
authors.forename: Kyungmin
authors.initials: K
authors.lastname: Hahm
authors.forename: Linda C
authors.initials: LC
authors.lastname: Burkly
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.forename: José
authors.initials: J
authors.lastname: Boucraut
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002462:Cell Membrane / Q000378:metabolism*; D000074049:Cytokine TWEAK; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid; D055815:Young Adult
chemical_list: D000074049:Cytokine TWEAK; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; C000613299:Tnfrsf12a protein, mouse; D048069:Tumor Necrosis Factors